MTOR-protein-interaction

Coevolutionary analysis of MTOR proteins G3BP1 and TSC2

The goal of this project is to pinpoint the location of the potential interaction sites on two proteins of the MTOR pathway, Ras GTPase-activating protein-binding protein 1 (G3BP1) and the tuberin subunit of tuberous sclerosis complex (TSC2), using mean-field direct coupling analysis (mfDCA).

MTOR Pathway and Roles of G3BP1 and TSC2

The MTOR signaling pathway, or mammalian mechanistic target of rapamycin pathway, is a master regulator and coordinator of cell growth, of which the inhibition/activation is crucial for oncological studies. The MTOR pathway is built up by signaling via its two sub-complexes, MTORC1 and MTORC2, and each has its own unique regulatory mechanisms. The proteins of interest in this project are involved in the function of MTORC1. MTORC1 regulation occurs at the lysosome, and is inhibited by TSC2 via an intermediate protein, Rheb. G3BP1, on the other hand, is known to be a key component of stress granules, bundles of RNA and protein that form in cells under stress, but has recently been experimentally shown to be highly likely involved in the binding of TSC2 to the lysosome - the question is: where?

Contents

1. Data: Fasta files, Hmmer profiles, and structure files for G3BP1 and TSC2
2. Images: Plots and visualisations of DCA results
3. Scripts: Simple ad-hoc python scripts to manipulate result files for visualisation purposes, analysis pipeline in progress
4. mfDCA: Original output of pydca's meanfield DCA implementation

Refer to the wiki for more information about the project.